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Clinical Significance of Annexin A2 Expression in Breast Cancer Patients.

Recent Research Articles from UNTHSC - Thu, 12/31/2020 - 08:01
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Clinical Significance of Annexin A2 Expression in Breast Cancer Patients.

Cancers (Basel). 2020 Dec 22;13(1):

Authors: Gibbs LD, Mansheim K, Maji S, Nandy R, Lewis CM, Vishwanatha JK, Chaudhary P

Abstract
Increasing evidence suggests that AnxA2 contributes to invasion and metastasis of breast cancer. However, the clinical significance of AnxA2 expression in breast cancer has not been reported. The expression of AnxA2 in cell lines, tumor tissues, and serum samples of breast cancer patients were analyzed by immunoblotting, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We found that AnxA2 was significantly upregulated in tumor tissues and serum samples of breast cancer patients compared with normal controls. The high expression of serum AnxA2 was significantly associated with tumor grades and poor survival of the breast cancer patients. Based on molecular subtypes, AnxA2 expression was significantly elevated in tumor tissues and serum samples of triple-negative breast cancer (TNBC) patients compared with other breast cancer subtypes. Our analyses on breast cancer cell lines demonstrated that secretion of AnxA2 is associated with its tyrosine 23 (Tyr23) phosphorylation in cells. The expression of non-phosphomimetic mutant of AnxA2 in HCC1395 cells inhibits its secretion from cells compared to wild-type AnxA2, which further suggest that Tyr23 phosphorylation is a critical step for AnxA2 secretion from TNBC cells. Our analysis of AnxA2 phosphorylation in clinical samples further confirmed that the phosphorylation of AnxA2 at Tyr23 was high in tumor tissues of TNBC patients compared to matched adjacent non-tumorigenic breast tissues. Furthermore, we observed that the diagnostic value of serum AnxA2 was significantly high in TNBC compared with other breast cancer subtypes. These findings suggest that serum AnxA2 concentration could be a potential diagnostic biomarker for TNBC patients.

PMID: 33374917 [PubMed]

Mutation of CEP72 Gene May Predispose Patients to Hepatotoxicity.

Recent Research Articles from UNTHSC - Thu, 12/31/2020 - 08:01
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Mutation of CEP72 Gene May Predispose Patients to Hepatotoxicity.

J Pediatr Hematol Oncol. 2020 10;42(7):e634-e636

Authors: Pham R, Hoeft A, Roberts C, Hamby T, Maloy C, Ray A

Abstract
Drug toxicities during treatment of acute lymphoblastic leukemia play a pivotal role in influencing the outcome as certain toxicities may impair treatment compliance. Polymorphisms in CEP72 have been linked to increased incidence of vincristine-induced toxicities, namely peripheral neuropathy. We hypothesize that polymorphisms in the same gene may increase a patient's risk of developing hepatotoxicity when receiving potentially hepatotoxic agents during chemotherapy. This report describes hepatotoxicity that first developed during consolidation in a patient homozygous for the CEP72 risk alleles. Bilirubin levels normalized following dose reduction of 6-mercaptopurine. The patient continues to tolerate maintenance therapy at a reduced dose of 6-mercaptopurine.

PMID: 31343483 [PubMed - indexed for MEDLINE]

Letter: Guidelines for the Management of Severe Traumatic Brain Injury: 2020 Update of the Decompressive Craniectomy Recommendations.

Recent Research Articles from UNTHSC - Tue, 12/29/2020 - 08:04
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Letter: Guidelines for the Management of Severe Traumatic Brain Injury: 2020 Update of the Decompressive Craniectomy Recommendations.

Neurosurgery. 2020 Dec 28;:

Authors: Dickerman R, Williamson J, Mathew E

PMID: 33370807 [PubMed - as supplied by publisher]

Modulation of astrocyte phenotype in response to T-cell interaction.

Recent Research Articles from UNTHSC - Tue, 12/29/2020 - 08:04
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Modulation of astrocyte phenotype in response to T-cell interaction.

J Neuroimmunol. 2020 Dec 18;351:577455

Authors: Hersh J, Prah J, Winters A, Liu R, Yang SH

Abstract
We determined that T-cell astrocyte interaction modulates interleukin-10 (IL-10) production from both cell types. The impact of IL-10 on astrocytes was compared to IL-10 generated from T-cell-astrocyte interactions in vitro. We demonstrated that T-cells directly interact with astrocytes to upregulate gene expression and secretion of IL-10, confirmed by elevated STAT3p/STAT3 expression in astrocytes. IL-10 increased astrocytes proliferation. In addition, IL-10 treatment and CD4+ co-culture shifts primary astrocytes toward a more energetic phenotype. These findings indicate that direct interaction of CD4+ T-cells with astrocytes, activated the IL-10 anti-inflammatory pathway, altering astrocyte phenotype, metabolism, and proliferation.

PMID: 33370671 [PubMed - as supplied by publisher]

The Role of Using HEART Score to Risk Stratify Chest Pain Among Emergency Department High Utilizers.

Recent Research Articles from UNTHSC - Tue, 12/29/2020 - 08:04
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The Role of Using HEART Score to Risk Stratify Chest Pain Among Emergency Department High Utilizers.

High Blood Press Cardiovasc Prev. 2020 Dec 28;:

Authors: Schrader CD, Meyering SH, Kumar D, Alanis N, D'Etienne JP, Shaikh S, Vo V, Kamaria AR, Huettner N, Wang H

Abstract
The HEART score is used to effectively risk stratify undifferentiated chest pain patients in the Emergency Department (ED). It is unclear whether such risk stratification can be applied among ED high utilizers. We aim to determine the efficacy and safety of using the HEART score to predict 30-day short-term major adverse cardiac events (MACE) in ED high utilizers. We conducted a retrospective, observational study in which ED high utilizers were defined as patients who had four or more ED visits within the past 12 months. ED high utilizers presenting at the study ED with chest pain were enrolled. Patients in which the HEART score was utilized were placed in the HEART group and patients with no HEART scores documented were placed to the usual care group. Hospital admissions and cardiac stress tests performed during the index hospitalizations, and 30-day MACE rates were analyzed and compared between the HEART and usual care groups. From January 1, 2017 to December 31, 2019, a total of 8,315 patient visits from ED high utilizers were enrolled. In the HEART group, 49% of ED visits were admitted with 20% receiving stress tests. A 30-day MACE outcome occurred among 1.4% of visits. In the usual care group, 44% of ED visits were admitted, with only 9% receiving index stress tests and a 1.5% of 30-day MACE occurrence (p=0.727). The study showed that similar short-term MACE outcomes occurred between patients using HEART scores and usual care to risk stratify chest pain among ED high utilizers.

PMID: 33369723 [PubMed - as supplied by publisher]

Pathophysiology of SARS-CoV-2 in Lung of Diabetic Patients.

Recent Research Articles from UNTHSC - Tue, 12/29/2020 - 08:04
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Pathophysiology of SARS-CoV-2 in Lung of Diabetic Patients.

Front Physiol. 2020;11:587013

Authors: Oliveira TL, Melo IS, Cardoso-Sousa L, Santos IA, El Zoghbi MB, Shimoura CG, Georjutti RP, Castro OW, Goulart LR, Jardim ACG, Cunha TM, Sabino-Silva R

Abstract
Novel coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its impact on patients with comorbidities is clearly related to fatality cases, and diabetes has been linked to one of the most important causes of severity and mortality in SARS-CoV-2 infected patients. Substantial research progress has been made on COVID-19 therapeutics; however, effective treatments remain unsatisfactory. This unmet clinical need is robustly associated with the complexity of pathophysiological mechanisms described for COVID-19. Several key lung pathophysiological mechanisms promoted by SARS-CoV-2 have driven the response in normoglycemic and hyperglycemic subjects. There is sufficient evidence that glucose metabolism pathways in the lung are closely tied to bacterial proliferation, inflammation, oxidative stress, and pro-thrombotic responses, which lead to severe clinical outcomes. It is also likely that SARS-CoV-2 proliferation is affected by glucose metabolism of type I and type II cells. This review summarizes the current understanding of pathophysiology of SARS-CoV-2 in the lung of diabetic patients and highlights the changes in clinical outcomes of COVID-19 in normoglycemic and hyperglycemic conditions.

PMID: 33362575 [PubMed]

Is there a Neurobiological Rationale for the Utility of the Iowa Gambling Task in Parkinson's Disease?

Recent Research Articles from UNTHSC - Tue, 12/29/2020 - 08:04
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Is there a Neurobiological Rationale for the Utility of the Iowa Gambling Task in Parkinson's Disease?

J Parkinsons Dis. 2020 Dec 23;:

Authors: Salvatore MF, Soto I, Alphonso H, Cunningham R, James R, Nejtek VA

Abstract
Up to 23% of newly diagnosed, non-demented, Parkinson's disease (PD) patients experience deficits in executive functioning (EF). In fact, EF deficits may occur up to 39-months prior to the onset of motor decline. Optimal EF requires working memory, attention, cognitive flexibility, and response inhibition underlying appropriate decision-making. The capacity for making strategic decisions requires inhibiting imprudent decisions and are associated with noradrenergic and dopaminergic signaling in prefrontal and orbitofrontal cortex. Catecholaminergic dysfunction and the loss of noradrenergic and dopaminergic cell bodies early in PD progression in the aforementioned cortical areas likely contribute to EF deficits resulting in non-strategic decision-making. Thus, detecting these deficits early in the disease process could help identify a significant portion of individuals with PD pathology (14-60%) before frank motor impairment. A task to evaluate EF in the domain of non-strategic decision-making might be useful to indicate the moderate loss of catecholamines that occurs early in PD pathology prior to motor decline and cognitive impairment. In this review, we focus on the potential utility of the Iowa Gambling Task (IGT) for this purpose, given significant overlap between in loss of dopaminergic and noradrenergic cells bodies in early PD and the deficits in catecholamine function associated with decreased EF. As such, given the loss of catecholamines already well-underway after PD diagnosis, we evaluate the potential utility of the IGT to identify the risk of therapeutic non-compliance and a potential companion approach to detect PD in premotor stages.

PMID: 33361612 [PubMed - as supplied by publisher]

Simple Nephrectomy in a Tertiary Care Safety Net Hospital - Patient Characteristics, Causes, Cost, and Renal Function Implications.

Recent Research Articles from UNTHSC - Tue, 12/29/2020 - 08:04
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Simple Nephrectomy in a Tertiary Care Safety Net Hospital - Patient Characteristics, Causes, Cost, and Renal Function Implications.

Urology. 2020 Dec 23;:

Authors: Ames KS, Baky F, Blair S, Sanchez J, Franklin W, Barefoot A, Mears J, Magness P, Johnson B, Bakare T, Hudak S, Antonelli J, Hutchinson R, Lotan Y, Woldu SL

Abstract
OBJECTIVE: To evaluate factors associated with simple nephrectomy at a safety net hospital with a diverse patient population and large catchment area. Simple nephrectomy is an underreported surgery. Performance of simple nephrectomy may represent a failure of management of underlying causes.
METHODS: We performed a retrospective review of simple nephrectomies performed at a major urban safety net hospital from 2014-2019. Detailed demographic, surgical, and renal functional outcomes were abstracted. We assessed the medical and social factors leading to performance of simple nephrectomy and report contemporaneous perception of preventability of the simple nephrectomy by the surgeon.
RESULTS: 85 patients underwent simple nephrectomy during the study period; 55% were non-white, 77% were women, and the median age at time of surgery was 46 years. The most common medical factors contributing to simple nephrectomy were stone disease in 55.3%, followed by retained ureteral stent (30.6%) and stricture (30.6%). The most common social factors were lack of insurance (58.5%), substance abuse issues (32.3%), mental health issues (24.6%), and immigration status (18.5%). In 38.8% of cases, the provider felt the surgery was preventable if medical factors leading to simple nephrectomy were properly addressed.
CONCLUSIONS: Simple nephrectomy is a common surgery in the safety net hospital setting. Both medical and sociologic factors can lead to simple nephrectomy, and awareness of these factors can lead efforts to mitigate them. This review has led to the implementation of strategies to minimize occurrences of retained stents in our patients.

PMID: 33359487 [PubMed - as supplied by publisher]

Evaluation of lead body burden in US adolescents.

Recent Research Articles from UNTHSC - Tue, 12/29/2020 - 08:04
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Evaluation of lead body burden in US adolescents.

Arch Environ Occup Health. 2020 Dec 28;:1-8

Authors: Ho WC, Lin YS, Caffrey JL, Faramawi MF

Abstract
The objective was to examine key determinants in the body burden of lead in adolescents as lead poisoning remains a major public health challenge. Data from 2,925 teenagers aged 12-18 older in the National Health and Nutrition Examination Survey (NHANES), 1999-2012 were analyzed. Lead in both blood and urine was significantly correlated among individuals. Despite higher blood lead in males, urinary lead measures corrected for dilution were similar between male and female adolescents. Thus, the urine-to-blood ratio was approximately 30% lower in male than female adolescents, suggesting that differences in renal disposal contributed to the greater body burden for young males. Differences in urinary lead disposal appear to be a key determinant in lead accumulation and thus, the degree of lead poisoning. Direct renal studies should be conducted to determine mechanisms and potential solutions.

PMID: 33357119 [PubMed - as supplied by publisher]

COVID-19 in China: Risk Factors and R0 Revisited.

Recent Research Articles from UNTHSC - Tue, 12/29/2020 - 08:04
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COVID-19 in China: Risk Factors and R0 Revisited.

Acta Trop. 2021 Jan;213:105731

Authors: Khan IM, Haque U, Zhang W, Zafar S, Wang Y, He J, Sun H, Lubinda J, Rahman MS

Abstract
The COVID-19 epidemic spread rapidly through China and subsequently proliferated globally leading to a pandemic situation around the globe. Human-to-human transmission, as well as asymptomatic transmission of the infection, have been confirmed. As of April 03, 2020, public health crisis in China due to COVID-19 was potentially under control. We compiled a daily dataset of case counts, mortality, recovery, temperature, population density, and demographic information for each prefecture during the period of January 11 to April 07, 2020. Understanding the characteristics of spatial clustering of the COVID-19 epidemic and R0 is critical in effectively preventing and controlling the ongoing global pandemic. Considering this, the prefectures were grouped based on several relevant features using unsupervised machine learning techniques. Subsequently, we performed a computational analysis utilizing the reported cases in China to estimate the revised R0 among different regions. Finally, our overall research indicates that the impact of temperature and demographic factors on virus transmission may be characterized using a stochastic transmission model. Such predictions will help in prevention planning in an ongoing global pandemic, prioritizing segments of a given community/region for action and providing a visual aid in designing prevention strategies for a specific geographic region. Furthermore, revised estimation and our methodology will aid in improving the human health consequences of COVID-19 elsewhere.

PMID: 33164890 [PubMed - indexed for MEDLINE]

The Association Between Depressive Symptoms and Accumulation of Stress Among Black Men in the Health and Retirement Study.

Recent Research Articles from UNTHSC - Tue, 12/29/2020 - 01:53
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The Association Between Depressive Symptoms and Accumulation of Stress Among Black Men in the Health and Retirement Study.

Innov Aging. 2020;4(5):igaa047

Authors: Thorpe RJ, Cobb R, King K, Bruce MA, Archibald P, Jones HP, Norris KC, Whitfield KE, Hudson D

Abstract
Background and Objectives: Among the multiple factors posited to drive the health inequities that black men experience, the fundamental role of stress in the production of poor health is a key component. Allostatic load (AL) is considered to be a byproduct of stressors related to cumulative disadvantage. Exposure to chronic stress is associated with poorer mental health including depressive symptoms. Few studies have investigated how AL contributes to depressive symptoms among black men. The purpose of the cross-sectional study was to examine the association between AL and depressive symptoms among middle- to old age black men.
Research Design and Methods: This project used the 2010 and 2012 wave of the Health and Retirement Study enhanced face-to-face interview that included a biomarker assessment and psychosocial questionnaire. Depressive symptoms, assessed by the endorsement of 3 or more symptoms on the Center for Epidemiological Studies-Depression 8-item scale, was the outcome variable. The main independent variable, AL, score was calculated by summing the number values that were in the high range for that particular biomarker value scores ranging from 0 to 7. black men whose AL score was 3 or greater were considered to be in the high AL group. Modified Poisson regression was used to estimate prevalence ratios (PRs) and corresponding 95% confidence intervals (CIs).
Results: There was a larger proportion of black men in the high AL group who reported depressive symptoms (30.0% vs. 20.0%) compared with black men in the low AL group. After adjusting for age, education, income, drinking, and smoking status, the prevalence of reporting 3 or more depressive symptoms was statistically significant among black men in the high AL group (PR = 1.61 [95% CI: 1.20-2.17]) than black men in the low AL group.
Discussion and Implications: Exposure to chronic stress is related to reporting 3 or more depressive symptoms among black men after controlling for potential confounders. Improving the social and economic conditions for which black men work, play, and pray is key to reducing stress, thereby potentially leading to the reporting of fewer depressive symptoms.

PMID: 33354627 [PubMed]

Effect of General Anesthesia on Cardiac Magnetic Resonance-Derived Cardiac Function in Repaired Tetralogy of Fallot.

Recent Research Articles from UNTHSC - Tue, 12/22/2020 - 05:14
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Effect of General Anesthesia on Cardiac Magnetic Resonance-Derived Cardiac Function in Repaired Tetralogy of Fallot.

Pediatr Cardiol. 2020 Dec;41(8):1660-1666

Authors: Muyskens S, Roshan T, Honan K, Umejiego J, Raynaud S, Ogunyankin F

Abstract
Cardiac magnetic resonance imaging (CMR)-derived ejection fraction (EF) predicts adverse outcomes in repaired tetralogy of Fallot (rTOF) and drives timing of pulmonary valve replacement. Certain patient populations require sedation for successful CMR image acquisition. General anesthesia (GA) has been shown to depress EF and heart rate (HR) in animal models, however, its effect on congenital heart disease is unknown. A retrospective review was conducted of all CMR patients referred with rTOF between January 2011 and May 2019. The cohort was separated into GA and non-GA groups. Propensity score matching (PSM) adjusted for selection bias. A kernel matching algorithm was used to match subjects and the differences in mean treatment effect on the treated were computed for left ventricular (LV) and right ventricular (RV) EF, HR, and cardiac index (CI). 143 patients met criteria, 37 patients under GA (mean age 15 years, range 2-45, 59% male), and 106 patients without GA (mean age 21 years, range 10-53, 50% male). Unmatched analysis showed significant depression of LV EF (50 vs. 57%, p < 0.001) and RV EF (42 vs. 48%, p < 0.001) in the GA group compared to the non-GA group. There was no significant difference in HR or CI. After matching and PSM adjustment, the GA group had a significant decrease in LV EF (49 vs. 56%, p < 0.001), RV EF (41 vs. 48%, p < 0.001), CI (2728 vs. 3701 ml/min/m2, p < 0.001), and HR (72 vs. 79 bpm, p = 0.04). General anesthesia with sevoflurane results in depressed CMR-derived EF.

PMID: 32740671 [PubMed - indexed for MEDLINE]

Comorbid patterns of anaemia and diarrhoea among children aged under 5 years in Ghana: a multivariate complex sample logistic regression analysis and spatial mapping visualisation.

Recent Research Articles from UNTHSC - Sat, 12/19/2020 - 08:01
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Comorbid patterns of anaemia and diarrhoea among children aged under 5 years in Ghana: a multivariate complex sample logistic regression analysis and spatial mapping visualisation.

Int Health. 2020 Dec 18;:

Authors: Duah HO, Amankwa CE, Adomako I, Owusu B, Agbadi P

Abstract
BACKGROUND: Anaemia and diarrhoea are known independent causes of under-five morbidity and mortality. This study sought to investigate predictors of comorbid patterns of anaemia and diarrhoea using the 2014 Ghana Demographic and Health Survey (GDHS).
METHODS: The study employed analysis of secondary data from the 2014 GDHS. We performed a multivariate complex sample logistic regression and spatial analysis.
RESULTS: The weighted prevalence of comorbid anaemia and diarrhoea was 9.28% with the highest burden (16.45%) found in the Upper West region. Independent predictors (risk factors) of comorbid patterns of anaemia and diarrhoea were children aged 6-23 mo (OR=2.17, 95% CI 1.42 to 3.33), male gender (OR=1.50, 95% C1 1.04 to 2.16), history of fever (OR=4.37, 95% CI 2.94 to 6.50) and living in a household with two children aged <5 y (OR=1.80, 95% CI 1.14 to 2.84). Protective factors were having a father with secondary or higher education (OR=0.57, 95% CI 0.33 to 0.97), living in a household with ≥6 members (OR=0.46, 95% CI 0.28 to 0.75) and living in a richer household (OR=0.38, 95% CI 0.16 to 0.89). Surface maps revealed inter-regional and subregional variations.
CONCLUSION: The study shows that the independent predictors of comorbid patterns of anaemia and diarrhoea among children aged <5 y in Ghana are age, gender, history of fever, the number of children aged <5 y in the household, parental education, household size and household wealth. The study identified zones to be targeted for cost-effective policy interventions.

PMID: 33339041 [PubMed - as supplied by publisher]

Plasma Total-Tau and Neurofilament Light Chain as Diagnostic Biomarkers of Alzheimer's Disease Dementia and Mild Cognitive Impairment in Adults with Down Syndrome.

Recent Research Articles from UNTHSC - Sat, 12/19/2020 - 08:01
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Plasma Total-Tau and Neurofilament Light Chain as Diagnostic Biomarkers of Alzheimer's Disease Dementia and Mild Cognitive Impairment in Adults with Down Syndrome.

J Alzheimers Dis. 2020 Dec 16;:

Authors: Petersen ME, Rafii MS, Zhang F, Hall J, Julovich D, Ances BM, Schupf N, Krinsky-McHale SJ, Mapstone M, Silverman W, Lott I, Klunk W, Head E, Christian B, Foroud T, Lai F, Diana Rosas H, Zaman S, Wang MC, Tycko B, Lee J, Handen B, Hartley S, Fortea J, O'Bryant S, Alzheimer’s Biomarker Consortium –Down Syndrome (ABC-DS)

Abstract
BACKGROUND: The need for diagnostic biomarkers of cognitive decline is particularly important among aging adults with Down syndrome (DS). Growing empirical support has identified the utility of plasma derived biomarkers among neurotypical adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD); however, the application of such biomarkers has been limited among the DS population.
OBJECTIVE: This study aimed to investigate the cross-sectional diagnostic performance of plasma neurofilament light chain (Nf-L) and total-tau, individually and in combination among a cohort of DS adults.
METHODS: Plasma samples were analyzed from n = 305 (n = 225 cognitively stable (CS); n = 44 MCI-DS; n = 36 DS-AD) participants enrolled in the Alzheimer's Biomarker Consortium -Down Syndrome.
RESULTS: In distinguishing DS-AD participants from CS, Nf-L alone produced an AUC of 90%, total-tau alone reached 74%, and combined reached an AUC of 86%. When age and gender were included, AUC increased to 93%. Higher values of Nf-L, total-tau, and age were all shown to be associated with increased risk for DS-AD. When distinguishing MCI-DS participants from CS, Nf-L alone produced an AUC of 65%, while total-tau alone reached 56%. A combined model with Nf-L, total-tau, age, and gender produced an AUC of 87%. Both higher values in age and total-tau were found to increase risk for MCI-DS; Nf-L levels were not associated with increased risk for MCI-DS.
CONCLUSION: Advanced assay techniques make total-tau and particularly Nf-L useful biomarkers of both AD pathology and clinical status in DS and have the potential to serve as outcome measures in clinical trials for future disease-modifying drugs.

PMID: 33337378 [PubMed - as supplied by publisher]

Potential for Kappa-Opioid Receptor Agonists to Engineer Nonaddictive Analgesics: A Narrative Review.

Recent Research Articles from UNTHSC - Fri, 12/18/2020 - 05:54
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Potential for Kappa-Opioid Receptor Agonists to Engineer Nonaddictive Analgesics: A Narrative Review.

Anesth Analg. 2020 Dec 16;:

Authors: Kaski SW, White AN, Gross JD, Siderovski DP

Abstract
A serious adverse effect of prescription opioid analgesics is addiction, both to these analgesics and to illicit drugs like heroin that also activate the µ-opioid receptor (MOR). Opioid use disorder (OUD) and opioid overdose deaths represent a current American health crisis, and the prescription of opioid analgesics has contributed significantly to this crisis. While prescription opioids are highly effective analgesics, there currently exists no facile way to use them for extended periods without the risk of addiction. If addiction caused by MOR-targeting analgesics could be blocked by blending in a new "antiaddiction" ingredient that does not diminish analgesia and does not introduce its own therapeutically limiting side effects, then continued clinical use of prescription opioids for treating pain could be maintained (or even enhanced) instead of curtailed. In this narrative review, we contextualize this hypothesis, first with a brief overview of the current American opioid addiction crisis. The neurobiology of 2 key receptors in OUD development, MOR and the κ-opioid receptor (KOR), is then discussed to highlight the neuroanatomical features and circuitry in which signal transduction from these receptors lie in opposition-creating opportunities for pharmacological intervention in curtailing the addictive potential of MOR agonism. Prior findings with mixed MOR/KOR agonists are considered before exploring new potential avenues such as biased KOR agonists. New preclinical data are highlighted, demonstrating that the G protein-biased KOR agonist nalfurafine reduces the rewarding properties of MOR-targeting analgesics and enhances MOR-targeting analgesic-induced antinociception. Finally, we discuss the recent discovery that a regulator of G protein signaling (namely, RGS12) is a key component of signaling bias at KOR, presenting another drug discovery target toward identifying a single agent or adjuvant to be added to traditional opioid analgesics that could reduce or eliminate the addictive potential of the latter drug.

PMID: 33332902 [PubMed - as supplied by publisher]

Editorial: Cancer Informatics Toward Precision Medicine.

Recent Research Articles from UNTHSC - Fri, 12/18/2020 - 05:54
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Editorial: Cancer Informatics Toward Precision Medicine.

Front Med (Lausanne). 2020;7:576611

Authors: Zhang F, Wu X, Chen W, Deng Y

PMID: 33330533 [PubMed]

Ablation of GSDMD Improves Outcome of Ischemic Stroke Through Blocking Canonical and Non-canonical Inflammasomes Dependent Pyroptosis in Microglia.

Recent Research Articles from UNTHSC - Fri, 12/18/2020 - 05:54
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Ablation of GSDMD Improves Outcome of Ischemic Stroke Through Blocking Canonical and Non-canonical Inflammasomes Dependent Pyroptosis in Microglia.

Front Neurol. 2020;11:577927

Authors: Wang K, Sun Z, Ru J, Wang S, Huang L, Ruan L, Lin X, Jin K, Zhuge Q, Yang S

Abstract
Ischemia/reperfusion (I/R) injury is a significant cause of mortality and long-term disability worldwide. Recent evidence has proved that pyroptosis, a novel cell death form, contributes to inflammation-induced neuron death and neurological function impairment following ischemic stroke. Gasdermin D (GSDMD) is a newly discovered key molecule of cell pyroptosis, but its biological function and precise role in ischemic stroke are still unclear. The present study investigates the cleavage activity of GSDMD, localization of pyroptotic cells, and global neuroinflammation in gsdmd -/- mice after I/R. The level of cell pyroptosis around the infarcted area was significantly increased in the acute phase of cerebral I/R injury. The ablation of GSDMD reduced the infraction volume and improved neurological function against cerebral I/R injury. Furthermore, we confirmed I/R injury induced cell pyroptosis mainly in microglia. Knockdown of GSDMD effectively inhibited the secretion of mature IL-1β and IL-18 from microglia cells but did not affect the expression of caspase-1/11 in vitro and in vivo. In summary, blocking GSDMD expression might serve as a potential therapeutic strategy for ischemic stroke.

PMID: 33329317 [PubMed]

Characterization of the Meal-Stimulated Incretin Response and Relationship With Structural Brain Outcomes in Aging and Alzheimer's Disease.

Recent Research Articles from UNTHSC - Fri, 12/18/2020 - 05:54
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Characterization of the Meal-Stimulated Incretin Response and Relationship With Structural Brain Outcomes in Aging and Alzheimer's Disease.

Front Neurosci. 2020;14:608862

Authors: Morris JK, John CS, Green ZD, Wilkins HM, Wang X, Kamat A, Swerdlow RS, Vidoni ED, Petersen ME, O'Bryant SE, Honea RA, Burns JM

Abstract
Background: Individuals with Alzheimer's Disease (AD) are often characterized by systemic markers of insulin resistance; however, the broader effects of AD on other relevant metabolic hormones, such as incretins that affect insulin secretion and food intake, remains less clear.
Methods: Here, we leveraged a physiologically relevant meal tolerance test to assess diagnostic differences in these metabolic responses in cognitively healthy older adults (CH; n = 32) and AD (n = 23) participants. All individuals also underwent a comprehensive clinical examination, cognitive evaluation, and structural magnetic resonance imaging.
Results: The meal-stimulated response of glucose, insulin, and peptide tyrosine tyrosine (PYY) was significantly greater in individuals with AD as compared to CH. Voxel-based morphometry revealed negative relationships between brain volume and the meal-stimulated response of insulin, C-Peptide, and glucose-dependent insulinotropic polypeptide (GIP) in primarily parietal brain regions.
Conclusion: Our findings are consistent with prior work that shows differences in metabolic regulation in AD and relationships with cognition and brain structure.

PMID: 33328877 [PubMed]

Prospects of Directly Reprogrammed Adult Human Neurons for Neurodegenerative Disease Modeling and Drug Discovery: iN vs. iPSCs Models.

Recent Research Articles from UNTHSC - Fri, 12/18/2020 - 05:54
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Prospects of Directly Reprogrammed Adult Human Neurons for Neurodegenerative Disease Modeling and Drug Discovery: iN vs. iPSCs Models.

Front Neurosci. 2020;14:546484

Authors: Zhang Y, Xie X, Hu J, Afreen KS, Zhang CL, Zhuge Q, Yang J

Abstract
A reliable disease model is critical to the study of specific disease mechanisms as well as for the discovery and development of new drugs. Despite providing crucial insights into the mechanisms of neurodegenerative diseases, translation of this information to develop therapeutics in clinical trials have been unsuccessful. Reprogramming technology to convert adult somatic cells to induced Pluripotent Stem Cells (iPSCs) or directly reprogramming adult somatic cells to induced Neurons (iN), has allowed for the creation of better models to understand the molecular mechanisms and design of new drugs. In recent times, iPSC technology has been commonly used for modeling neurodegenerative diseases and drug discovery. However, several technological challenges have limited the application of iN. As evidence suggests, iN for the modeling of neurodegenerative disorders is advantageous compared to those derived from iPSCs. In this review, we will compare iPSCs and iN models for neurodegenerative diseases and their potential applications in the future.

PMID: 33328842 [PubMed]

School-entry requirements for HPV vaccination: part of the patchwork for HPV-related cancer prevention.

Recent Research Articles from UNTHSC - Fri, 12/18/2020 - 05:54
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School-entry requirements for HPV vaccination: part of the patchwork for HPV-related cancer prevention.

Hum Vaccin Immunother. 2020 Dec 17;:1-5

Authors: Thompson EL, Daley EM, Washburn T, Salisbury-Keith K, Saslow D, Fontenot HB, Zimet GD

Abstract
Human papillomavirus (HPV) vaccination can prevent six types of HPV-related cancers, and approximately, 54.2% of adolescents are up-to-date with the HPV vaccine in the United States. While moderate success has been achieved with provider- and parent-focused interventions, HPV vaccination in the U.S. lags well behind desired goals. In order to maximize HPV vaccination and prevention of HPV-related cancers, it may be prudent to consider state policy approaches, such as school-entry requirements as part of the patchwork of provider, parent, and structural interventions. In this paper, we reviewed the history of efforts to implement school-entry requirements for HPV vaccine, the challenges and benefits associated with implementing these requirements, and the evidence for the effectiveness of school-entry requirements. In addition, we presented new data from Rhode Island's Immunization Information System (IIS) showing how their school-entry requirement, implemented in 2015, has impacted HPV vaccination rates. These registry data indicate that HPV vaccination rates improved significantly after the 2014-2015 school year and policy implementation, and add to the ongoing evidence supporting the value of school-entry requirements for HPV vaccination. School-entry requirements should be considered alongside other initiatives and policies for promoting HPV vaccine uptake. Taking a comprehensive systems approach to HPV vaccination is needed.

PMID: 33327839 [PubMed - as supplied by publisher]

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